U.S. Pat. No. 5,112,975 (EP 0 158 476) discloses processes using morphine as starting material for manufacturing noroxymorphone. This 6-step process is illustrated in scheme 1.

Whereas the general outlay of the process looks attracting major drawbacks are noticed when reading the teachings as disclosed for the individual steps.
Step 1 is executed with the problematic solvent chloroform. According to the European Medicines Agency's Q3C (R4) Guideline for Residual Solvents chloroform is a highly problematic solvent that can only be tolerated in medical compositions in a maximal concentration of 60 ppm.
Step 2 is executed with Jones' reagent, a Cr(VI) reagent bearing an inherent risk for both product safety and environment. An alternate methodology is disclosed by Schwartz in FR 2 515 184 (U.S. Pat. No. 4,795,813). N-ethoxycarbonylnorcodeine (compound III) may be oxidized by manganese dioxide. However, oxidations with manganese dioxide are very sensitive to the nature of the reagent, which widely varies for commercially available material. Typically a huge excess of manganese dioxide is needed (Ninan A.; Sainsbury M. (1992). “An improved synthesis of noroxymorphone”, Tetrahedron 48 (11): 6709) making this process costly and generating significant amounts of wastes.
For step 4 FR 2 515 184 discloses that peracids may be used for this transformation. The peracids may be either formed in situ by mixing hydrogen peroxide with acids or acid anhydrides or be used as isolated compounds. Isolated peracids are hazardous compounds due to their intrinsic nature to decompose. Therefore handling and storing these compounds is demanding. In situ generated peracids overcome the storage and transport problems however, reported yields for simple organic acids such as acetic and formic acids are low (38% and 33%, respectively). Maleic acid would allow higher yields; however, additional solvents are needed.
For step 6 FR 2 515 184 reports as being performed with moderate yield only. The di-ethoxycarbonyl compound yields 60% noroxymorphone only. This may be due to the harsh reaction conditions needed for the hydrolysis of the ethoxycarbonyl amide moiety. More gentle conditions can be used if alternate oxycarbonyl amide compounds are used. However, viable substitutes such as alpha-chloroethoxycarbonyl amide are significantly more expensive see for example Peter G. M. Wuts, Theodora W. Greene: “Green's Protective Groups in Organic Synthesis”, 4th Ed., John Wiley & Sons Inc., Hoboken, N.J.).
The reported overall yield in FR 2 515 184 for the 6 step synthesis does not exceed 37%.
The overall yield of 37% for reactions of the state of the art is asking for further investigations to improve ecological and economic aspects of the process and to reduce the use of toxic agents and solvents.
Hence, there is still a need for an improved process for producing noroxymorphone from morphine.